Lymphatic vessels interact dynamically with the hair follicle stem cell niche during skin regeneration in vivo

TY - JOUR

T1 - Lymphatic vessels interact dynamically with the hair follicle stem cell niche during skin regeneration in vivo

AU - Peña-Jimenez, Daniel

AU - Fontenete, Silvia

AU - Megias, Diego

AU - Fustero-Torre, Coral

AU - Graña-Castro, Osvaldo

AU - Castellana, Donatello

AU - Loewe, Robert

AU - Perez-Moreno, Mirna

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Lymphatic vessels are essential for skin fluid homeostasis and immune cell trafficking. Whether the lymphatic vasculature is associated with hair follicle regeneration is, however, unknown. Here, using steady and live imaging approaches in mouse skin, we show that lymphatic vessels distribute to the anterior permanent region of individual hair follicles, starting from development through all cycle stages and interconnecting neighboring follicles at the bulge level, in a stem cell-dependent manner. Lymphatic vessels further connect hair follicles in triads and dynamically flow across the skin. At the onset of the physiological stem cell activation, or upon pharmacological or genetic induction of hair follicle growth, lymphatic vessels transiently expand their caliber suggesting an increased tissue drainage capacity. Interestingly, the physiological caliber increase is associated with a distinct gene expression correlated with lymphatic vessel reorganization. Using mouse genetics, we show that lymphatic vessel depletion blocks hair follicle growth. Our findings point toward the lymphatic vasculature being important for hair follicle development, cycling, and organization, and define lymphatic vessels as stem cell niche components, coordinating connections at tissue-level, thus provide insight into their functional contribution to skin regeneration.

AB - Lymphatic vessels are essential for skin fluid homeostasis and immune cell trafficking. Whether the lymphatic vasculature is associated with hair follicle regeneration is, however, unknown. Here, using steady and live imaging approaches in mouse skin, we show that lymphatic vessels distribute to the anterior permanent region of individual hair follicles, starting from development through all cycle stages and interconnecting neighboring follicles at the bulge level, in a stem cell-dependent manner. Lymphatic vessels further connect hair follicles in triads and dynamically flow across the skin. At the onset of the physiological stem cell activation, or upon pharmacological or genetic induction of hair follicle growth, lymphatic vessels transiently expand their caliber suggesting an increased tissue drainage capacity. Interestingly, the physiological caliber increase is associated with a distinct gene expression correlated with lymphatic vessel reorganization. Using mouse genetics, we show that lymphatic vessel depletion blocks hair follicle growth. Our findings point toward the lymphatic vasculature being important for hair follicle development, cycling, and organization, and define lymphatic vessels as stem cell niche components, coordinating connections at tissue-level, thus provide insight into their functional contribution to skin regeneration.

KW - hair cycle

KW - hair follicle

KW - lymphatic vessels

KW - skin

KW - stem cells

U2 - 10.15252/embj.2019101688

DO - 10.15252/embj.2019101688

M3 - Journal article

C2 - 31475747

AN - SCOPUS:85071888072

SN - 0261-4189

VL - 38

JO - EMBO Journal

JF - EMBO Journal

IS - 19

M1 - e101688

ER -